Transformation of malaria parasites by the spontaneous uptake and expression of DNA from human erythrocytes

The uptake and expression of extracellular DNA has been established as a me chanism for horizontal transfer of genes between bacterial species. Such tr ansfer can support acquisition of advantageous elements, including determin ants that affect the interactions between infectious organisms and their ho sts. Here we show that erythrocyte-stage Plasmodium falciparum malaria para sites spontaneously take up DNA from the host cell cytoplasm into their nuc lei. We have exploited this finding to produce levels of reporter expressio n in P.falciparum that are substantially improved over those obtained by el ectroporation protocols currently used to transfect malaria parasites, Para sites were transformed to a drug-resistant state when placed into cell cult ure with erythrocytes containing a plasmid encoding the human dihydrofolate reductase sequence. The findings reported here suggest that the malaria ge nome may be continually exposed to exogenous DNA from residual nuclear mate rial in host erythrocytes.